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[PMID]:29408309
[Au] Autor:Mohamed DI; Nabih ES; El-Waseef DAA; El-Kharashi OA; Abd El Samad AA
[Ad] Endereço:Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
[Ti] Título:The protective effect of pentoxifylline versus silymarin on the pancreas through increasing adenosine by CD39 in a rat model of liver cirrhosis: Pharmacological, biochemical and histological study.
[So] Source:Gene;651:9-22, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Impaired glucose homoeostasis due to insulin resistance and decrease sensitivity of pancreatic ß-cells is a feature of liver disease and results into hepatogenous diabetes. Decrease expression of CD39 was linked to inflammation and occurrence of diabetes. Therefore, we performed this study to explore the protective effect of pentoxifylline (PTX) and silymarin administration on the ß-cells of the pancreas in a rat model of thioacetamide induced liver cirrhosis. Biochemical, histological and immunohistochemistry studies of the liver and pancreas were performed and provided an evidence on the protective effect of PTX to pancreatic ß-cells compared to silymarin. Also, silymarin induced a significant improvement of liver cirrhosis compared to PTX. In conclusion, the potential protective effect of PTX against ß-cells deterioration could be attributed to increasing pancreatic CD39 expression and the subsequent increase of adenosine.
[Mh] Termos MeSH primário: Adenosina/metabolismo
Antígenos CD/metabolismo
Apirase/metabolismo
Cirrose Hepática Experimental/tratamento farmacológico
Pâncreas/efeitos dos fármacos
Pentoxifilina/uso terapêutico
Substâncias Protetoras/uso terapêutico
Silimarina/uso terapêutico
[Mh] Termos MeSH secundário: Amilases/sangue
Animais
Modelos Animais de Doenças
Células Secretoras de Insulina/efeitos dos fármacos
Fígado/patologia
Cirrose Hepática Experimental/metabolismo
Cirrose Hepática Experimental/patologia
Testes de Função Hepática
Masculino
Pâncreas/patologia
Ratos
Ratos Wistar
Fator de Crescimento Transformador beta1/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Protective Agents); 0 (Silymarin); 0 (Transforming Growth Factor beta1); EC 3.2.1.- (Amylases); EC 3.6.1.5 (Apyrase); EC 3.6.1.5 (CD39 antigen); K72T3FS567 (Adenosine); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


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[PMID]:29318581
[Au] Autor:Vietto V; Franco JV; Saenz V; Cytryn D; Chas J; Ciapponi A
[Ad] Endereço:Family and Community Medicine Service, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
[Ti] Título:Prostanoids for critical limb ischaemia.
[So] Source:Cochrane Database Syst Rev;1:CD006544, 2018 01 10.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular disease in the general population. Although numerous treatments have been adopted for patients at different disease stages, no option other than amputation is available for patients presenting with critical limb ischaemia (CLI) unsuitable for rescue or reconstructive intervention. In this regard, prostanoids have been proposed as a therapeutic alternative, with the aim of increasing blood supply to the limb with occluded arteries through their vasodilatory, antithrombotic, and anti-inflammatory effects. This is an update of a review first published in 2010. OBJECTIVES: To determine the effectiveness and safety of prostanoids in patients with CLI unsuitable for rescue or reconstructive intervention. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (January 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). In addition, we searched trials registries (January 2017) and contacted pharmaceutical manufacturers, in our efforts to identify unpublished data and ongoing trials. SELECTION CRITERIA: Randomised controlled trials describing the efficacy and safety of prostanoids compared with placebo or other pharmacological control treatments for patients presenting with CLI without chance of rescue or reconstructive intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. We resolved disagreements by consensus or by consultation with a third review author. MAIN RESULTS: For this update, 15 additional studies fulfilled selection criteria. We included in this review 33 randomised controlled trials with 4477 participants; 21 compared different prostanoids versus placebo, seven compared prostanoids versus other agents, and five conducted head-to-head comparisons using two different prostanoids.We found low-quality evidence that suggests no clear difference in the incidence of cardiovascular mortality between patients receiving prostanoids and those given placebo (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.41 to 1.58). We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared with placebo (RR 0.97, 95% CI 0.86 to 1.09). Adverse events were more frequent with prostanoids than with placebo (RR 2.11, 95% CI 1.79 to 2.50; moderate-quality evidence). The most commonly reported adverse events were headache, nausea, vomiting, diarrhoea, flushing, and hypotension. We found moderate-quality evidence showing that prostanoids reduced rest-pain (RR 1.30, 95% CI 1.06 to 1.59) and promoted ulcer healing (RR 1.24, 95% CI 1.04 to 1.48) when compared with placebo, although these small beneficial effects were diluted when we performed a sensitivity analysis that excluded studies at high risk of bias. Additionally, we found evidence of low to very low quality suggesting the effects of prostanoids versus other active agents or versus other prostanoids because studies conducting these comparisons were few and we judged them to be at high risk of bias. None of the included studies assessed quality of life. AUTHORS' CONCLUSIONS: We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared against placebo. Moderate-quality evidence showed small beneficial effects of prostanoids for rest-pain relief and ulcer healing when compared with placebo. Additionally, moderate-quality evidence showed a greater incidence of adverse effects with the use of prostanoids, and low-quality evidence suggests that prostanoids have no effect on cardiovascular mortality when compared with placebo. None of the included studies reported quality of life measurements. The balance between benefits and harms associated with use of prostanoids in patients with critical limb ischaemia with no chance of reconstructive intervention is uncertain; therefore careful assessment of therapeutic alternatives should be considered. Main reasons for downgrading the quality of evidence were high risk of attrition bias and imprecision of effect estimates.
[Mh] Termos MeSH primário: Isquemia/tratamento farmacológico
Perna (Membro)/irrigação sanguínea
Doenças Vasculares Periféricas/tratamento farmacológico
Prostaglandinas/uso terapêutico
[Mh] Termos MeSH secundário: Alprostadil/uso terapêutico
Amputação/estatística & dados numéricos
Epoprostenol/uso terapêutico
Seres Humanos
Iloprosta/uso terapêutico
Isquemia/mortalidade
Perna (Membro)/cirurgia
Úlcera da Perna/tratamento farmacológico
Nafronil/uso terapêutico
Ácidos Nicotínicos/uso terapêutico
Pentoxifilina/uso terapêutico
Prostaglandinas/efeitos adversos
Ensaios Clínicos Controlados Aleatórios como Assunto
Vasodilatadores/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Nicotinic Acids); 0 (Prostaglandins); 0 (Vasodilator Agents); 42H8PQ0NMJ (Nafronyl); A99MK953KZ (Inositol Niacinate); DCR9Z582X0 (Epoprostenol); F5TD010360 (Alprostadil); JED5K35YGL (Iloprost); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD006544.pub3


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Monteiro, Hugo Pequeno
Texto completo SciELO Brasil
[PMID]:29236798
[Au] Autor:Oliveira TRR; Oliveira GF; Simões RS; Feitosa SM; Tikazawa EH; Monteiro HP; Fagundes DJ; Taha MO
[Ad] Endereço:PhD, Associate Professor, School of Health Sciences, Universidade Federal da Grande Dourados (UFGD), Brazil. Acquisition, analysis and interpretation of data; technical procedures; statistical analysis; manuscript preparation and writing.
[Ti] Título:The expression of endothelial and inducible nitric oxide synthase and apoptosis in intestinal ischemia and reperfusion injury under the action of ischemic preconditioning and pentoxifylline.
[So] Source:Acta Cir Bras;32(11):935-948, 2017 Nov.
[Is] ISSN:1678-2674
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To investigate the expression of nitric oxide synthase (NOS) and apoptosis associated with ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal ischemia (I) and reperfusion (R) injury. METHODS: Thirty male rats were assigned to 5 groups: (CG), no clamping of the superior mesenteric artery (90 minutes); (IR-SS) saline + ischemia (30 minutes) + reperfusion (60 minutes); (IR-PTX) PTX + ischemia (30 minutes) + reperfusion (60 minutes); (IPC-IR-SS) 5 minutes of ischemia + 5 minutes of reperfusion (IPC) + saline + I(30 minutes)+R(60 minutes); and (IPC-IR-PTX) IPC + PTX + I(30 minutes)+ R(60 minutes). RESULTS: The application of IPC and PTX showed a significantly lower immunohistochemistry reaction for active caspase-3 (P<0.05) compared to IR+SS. The number of cells immunoreactive to BCL-2 was higher in the IR-PTX group (P>0.05). The NOS-2 expression (qRTPCR) in the IR-PTX group (P<0.05) was higher than the values for the IPC+IR-SS and IPC-IR-PTX groups. The NOS-3 expression was significantly upper in the IPC-IR-PTX group than in the CG (P<0.05), the IR-SS (P<0.05) and the IR-PTX (P<0.05) groups. CONCLUSIONS: The BCL-2 and active caspase-3 showed beneficial effects on PTX and IPC. The expression of NOS-2 and NOS-3 in the IPC and IPC-PTX groups showed no synergistic effect.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Enteropatias/prevenção & controle
Intestinos/irrigação sanguínea
Precondicionamento Isquêmico
Óxido Nítrico Sintase/metabolismo
Pentoxifilina/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Apoptose/fisiologia
Modelos Animais de Doenças
Seres Humanos
Imuno-Histoquímica
Enteropatias/enzimologia
Intestinos/patologia
Masculino
RNA Mensageiro/análise
Ratos
Ratos Wistar
Vasodilatadores/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (Vasodilator Agents); EC 1.14.13.39 (Nitric Oxide Synthase); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE


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[PMID]:28455156
[Au] Autor:Nabi A; Khalili MA; Fesahat F; Talebi A; Ghasemi-Esmailabad S
[Ad] Endereço:Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
[Ti] Título:Pentoxifylline increase sperm motility in devitrified spermatozoa from asthenozoospermic patient without damage chromatin and DNA integrity.
[So] Source:Cryobiology;76:59-64, 2017 Jun.
[Is] ISSN:1090-2392
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The freeze-thaw process results in reduced motility, viability and fertilization potential of human spermatozoa. So, a variety of substances were evaluated in order to enhance human sperm resistance to the stress of cryopreservation, such as Pentoxifylline (PTX) for improving the Intracytoplasmic sperm injection (ICSI) outcomes. The aim was to investigate the effect of PTX on sperm parameters and chromatin/DNA integrity of asthenozoospermic semen post vitrification. A total of 30 semen specimens were obtained from infertile men with asthenozoospermia. The cryoprotectant-free vitrification was performed for the samples after assessment of sperm parameters. After warming, each sample was exposed for 30 min to 3.6 mmol/l PTX in experimental group and the control group without any treatment apposing at 37 °C for 30 min in regard, to repeat all in vitro analysis (sperm parameters and DNA integrity assay). Regardless of the vitrification devastating impacts on sperm parameters, incubation of post vitrified samples with PTX increased the rate of progressive motility (P < 0.01). Moreover, PTX addition did not significantly damage DNA integrity of asthenozoospermic sperm samples. The data showed that PTX was able to improve sperm movement without any adverse effects on sperm chromatin/DNA integrity in vitrification program.
[Mh] Termos MeSH primário: Criopreservação
Pentoxifilina/farmacologia
Preservação do Sêmen
Espermatozoides
Vitrificação
[Mh] Termos MeSH secundário: Adulto
Astenozoospermia
Cromatina
Dano ao DNA
Seres Humanos
Masculino
Meia-Idade
Injeções de Esperma Intracitoplásmicas
Motilidade Espermática/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:28783300
[Au] Autor:Fiorentini F; Romero E; Fraaije MW; Faber K; Hall M; Mattevi A
[Ad] Endereço:Austrian Centre of Industrial Biotechnology, c/o Department of Chemistry, University of Graz , Heinrichstrasse 28, 8010 Graz, Austria.
[Ti] Título:Baeyer-Villiger Monooxygenase FMO5 as Entry Point in Drug Metabolism.
[So] Source:ACS Chem Biol;12(9):2379-2387, 2017 Sep 15.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Flavin-containing monooxygenases (FMOs) are emerging as effective players in oxidative drug metabolism. Until recently, the functions of the five human FMO isoforms were mostly linked to their capability of oxygenating molecules containing soft N- and S-nucleophiles. However, the human FMO isoform 5 was recently shown to feature an atypical activity as Baeyer-Villiger monooxygenase. With the aim of evaluating such an alternative entry point in the metabolism of active pharmaceutical ingredients, we selected and tested drug molecules bearing a carbonyl group on an aliphatic chain. Nabumetone and pentoxifylline, two widely used pharmaceuticals, were thereby demonstrated to be efficiently oxidized in vitro by FMO5 to the corresponding acetate esters with high selectivity. The proposed pathways explain the formation of a predominant plasma metabolite of pentoxifylline as well as the crucial transformation of the pro-drug nabumetone into the pharmacologically active compound. Using the recombinant enzyme, the ester derivatives of both drugs were obtained in milligram amounts, purified, and fully characterized. This protocol can potentially be extended to other FMO5 candidate substrates as it represents an effective and robust bench-ready platform applicable to API screening and metabolite synthesis.
[Mh] Termos MeSH primário: Butanonas/metabolismo
Inibidores de Ciclo-Oxigenase 2/metabolismo
Oxigenases/metabolismo
Pentoxifilina/metabolismo
Inibidores de Fosfodiesterase/metabolismo
[Mh] Termos MeSH secundário: Seres Humanos
Peróxido de Hidrogênio/metabolismo
Oxirredução
Preparações Farmacêuticas/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Butanones); 0 (Cyclooxygenase 2 Inhibitors); 0 (Pharmaceutical Preparations); 0 (Phosphodiesterase Inhibitors); BBX060AN9V (Hydrogen Peroxide); EC 1.13.- (Oxygenases); EC 1.14.13.8 (dimethylaniline monooxygenase (N-oxide forming)); LW0TIW155Z (nabumetone); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170808
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00470


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[PMID]:28752910
[Au] Autor:Showell MG; Mackenzie-Proctor R; Jordan V; Hart RJ
[Ad] Endereço:Department of Obstetrics and Gynaecology, University of Auckland, Park Road Grafton, Auckland, New Zealand, 1142.
[Ti] Título:Antioxidants for female subfertility.
[So] Source:Cochrane Database Syst Rev;7:CD007807, 2017 07 28.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility. OBJECTIVES: To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women. SEARCH METHODS: We searched the following databases (from their inception to September 2016) with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, the Cochrane Central Register of Studies (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of appropriate studies and searched for ongoing trials in the clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible studies, extracted the data and assessed the risk of bias of the included studies. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events. We pooled studies using a fixed-effect model, and calculated odds ratios (ORs) with 95% confidence intervals (CIs) for the dichotomous outcomes of live birth, clinical pregnancy and adverse events. We assessed the overall quality of the evidence by applying GRADE criteria. MAIN RESULTS: We included 50 trials involving 6510 women. Investigators compared oral antioxidants, including combinations of antioxidants, N-acetyl-cysteine, melatonin, L-arginine, myo-inositol, D-chiro-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, pentoxifylline and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant.Very low-quality evidence suggests that antioxidants may be associated with an increased live birth rate compared with placebo or no treatment/standard treatment (OR 2.13, 95% CI 1.45 to 3.12, P > 0.001, 8 RCTs, 651 women, I = 47%). This suggests that among subfertile women with an expected live birth rate of 20%, the rate among women using antioxidants would be between 26% and 43%.Very low-quality evidence suggests that antioxidants may be associated with an increased clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.52, 95% CI 1.31 to 1.76, P < 0.001, 26 RCTs, 4271 women, I = 66%). This suggests that among subfertile women with an expected clinical pregnancy rate of 22%, the rate among women using antioxidants would be between 27% and 33%. Heterogeneity was moderately high.There was insufficient evidence to determine whether there was a difference between the groups in rates of miscarriage (OR 0.79, 95% CI 0.58 to 1.08, P = 0.14, 18 RCTs, 2834 women, I = 23%, very low quality evidence). This suggests that, among subfertile women with an expected miscarriage rate of 7%, use of antioxidants would be expected to result in a miscarriage rate of between 4% and 7%. There was also insufficient evidence to determine whether there was a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.73 to 1.38, P = 0.98, 8 RCTs, 2163 women, I = 4%, very low quality evidence). This suggests that among subfertile women with an expected multiple pregnancy rate of 8%, use of antioxidants would be expected to result in a multiple pregnancy rate between 6% and 11%. Likewise, there was insufficient evidence to determine whether there was a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10, P = 0.47, 3 RCTs, 343 women, I = 0%, very low quality evidence). This suggests that among subfertile women with an expected gastrointestinal disturbance rate of 2%, use of antioxidants would be expected to result in a rate between 1% and 11%. Overall adverse events were reported by 35 trials in the meta-analysis, but there was insufficient evidence to draw any conclusions.Only one trial reported on live birth, clinical pregnancy or adverse effects in the antioxidant versus antioxidant comparison, and no conclusions could be drawn.Very low-quality evidence suggests that pentoxifylline may be associated with an increased clinical pregnancy rate compared with placebo or no treatment (OR 2.07, 95% CI 1.20 to 3.56, P = 0.009, 3 RCTs, 276 women, I = 0%). This suggests that among subfertile women with an expected clinical pregnancy rate of 25%, the rate among women using pentoxifylline would be between 28% and 53%.There was insufficient evidence to determine whether there was a difference between the groups in rates of miscarriage (OR 1.34, 95% CI 0.46 to 3.90, P = 0.58, 3 RCTs, 276 women, I = 0%) or multiple pregnancy (OR 0.78, 95% CI 0.20 to 3.09, one RCT, 112 women, very low quality evidence). This suggests that among subfertile women with an expected miscarriage rate of 4%, the rate among women using pentoxifylline would be between 2% and 15%. For multiple pregnancy, the data suggest that among subfertile women with an expected multiple pregnancy rate of 9%, the rate among women using pentoxifylline would be between 2% and 23%.The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency. AUTHORS' CONCLUSIONS: In this review, there was very low-quality evidence to show that taking an antioxidant may provide benefit for subfertile women, but insufficient evidence to draw any conclusions about adverse events. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women.
[Mh] Termos MeSH primário: Antioxidantes/administração & dosagem
Infertilidade Feminina/tratamento farmacológico
[Mh] Termos MeSH secundário: Aborto Espontâneo/epidemiologia
Administração Oral
Antioxidantes/efeitos adversos
Feminino
Seres Humanos
Nascimento Vivo/epidemiologia
Estresse Oxidativo
Pentoxifilina/efeitos adversos
Pentoxifilina/uso terapêutico
Gravidez
Taxa de Gravidez
Gravidez Múltipla
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antioxidants); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD007807.pub3


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[PMID]:28704725
[Au] Autor:Italiya KS; Sharma S; Kothari I; Chitkara D; Mittal A
[Ad] Endereço:Industrial Research Laboratory (IRL), Department of Pharmacy, Birla Institute of Technology and Science (BITS-PILANI), Pilani, Rajasthan, 333031, India.
[Ti] Título:Simultaneous estimation of lisofylline and pentoxifylline in rat plasma by high performance liquid chromatography-photodiode array detector and its application to pharmacokinetics in rat.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1061-1062:49-56, 2017 Sep 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Lisofylline (LSF) is an anti-inflammatory and immunomodulatory agent with proven activity in serious infections associated with cancer chemotherapy, hyperoxia-induced acute lung injury, autoimmune disorders including type-1 diabetes (T1DM) and islet rejection after islet transplantation. It is also an active metabolite of another anti-inflammatory agent, Pentoxifylline (PTX). LSF bears immense therapeutic potential in multiple pharmacological activities and hence appropriate and accurate quantification of LSF is very important. Although a number of analytical methods for quantification of LSF and PTX have been reported for pharmacokinetics and metabolic studies, each of these have certain limitations in terms of large sample volume required, complex extraction procedure and/or use of highly sophisticated instruments like LC-MS/MS. The aim of current study is to develop a simple reversed-phase HPLC method in rat plasma for simultaneous determination of LSF and PTX with the major objective of ensuring minimum sample volume, ease of extraction, economy of analysis, selectivity and avoiding use of instruments like LC-MS/MS to ensure a widespread application of the method. A simple liquid-liquid extraction method using methylene chloride as extracting solvent was used for extracting LSF and PTX from rat plasma (200µL). Samples were then evaporated, reconstituted with mobile phase and injected into HPLC coupled with photo-diode detector (PDA). LSF, PTX and 3-isobutyl 1-methyl xanthine (IBMX, internal standard) were separated on Inertsil® ODS (C18) column (250×4.6mm, 5µm) with mobile phase consisting of A-methanol B-water (50:50v/v) run in isocratic mode at flow rate of 1mL/min for 15min and detection at 273nm. The method showed linearity in the concentration range of 50-5000ng/mL with LOD of 10ng/mL and LLOQ of 50ng/mL for both LSF and PTX. Weighted linear regression analysis was also performed on the calibration data. The mean absolute recoveries were found to be 80.47±3.44 and 80.89±3.73% for LSF and PTX respectively. The method was successfully applied for studying the pharmacokinetics of LSF and PTX after IV bolus administration at dose of 25mg/kg in Wistar rat. In conclusion, a simple, sensitive, accurate and precise reversed-phase HPLC-UV method was established for simultaneous determination of LSF and PTX in rat plasma.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Pentoxifilina/análogos & derivados
Pentoxifilina/sangue
Pentoxifilina/farmacocinética
[Mh] Termos MeSH secundário: Animais
Estabilidade de Medicamentos
Limite de Detecção
Modelos Lineares
Masculino
Pentoxifilina/química
Ratos
Ratos Wistar
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
L1F2Q2X956 (lisofylline); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170714
[St] Status:MEDLINE


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[PMID]:28641684
[Au] Autor:McLaughlin MF; Donoviel DB; Jones JA
[Ti] Título:Novel Indications for Commonly Used Medications as Radiation Protectants in Spaceflight.
[So] Source:Aerosp Med Hum Perform;88(7):665-676, 2017 Jul 01.
[Is] ISSN:2375-6314
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In the space environment, the traditional radioprotective principles of time, distance, and shielding become difficult to implement. Additionally, the complex radiation environment inherent in space, the chronic exposure timeframe, and the presence of numerous confounding variables complicate the process of creating appropriate risk models for astronaut exposure. Pharmaceutical options hold tremendous promise to attenuate acute and late effects of radiation exposure in the astronaut population. Pharmaceuticals currently approved for other indications may also offer radiation protection, modulation, or mitigation properties along with a well-established safety profile. Currently there are only three agents which have been clinically approved to be employed for radiation exposure, and these only for very narrow indications. This review identifies a number of agents currently approved by the U.S. Food and Drug Administration (FDA) which could warrant further investigation for use in astronauts. Specifically, we examine preclinical and clinical evidence for statins, nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), metformin, calcium channel blockers, ß adrenergic receptor blockers, fingolimod, N-acetylcysteine, and pentoxifylline as potential radiation countermeasures.McLaughlin MF, Donoviel DB, Jones JA. Novel indications for commonly used medications as radiation protectants in spaceflight. Aerosp Med Hum Perform. 2017; 88(7):665-676.
[Mh] Termos MeSH primário: Astronautas
Lesões por Radiação/prevenção & controle
Protetores contra Radiação/uso terapêutico
Voo Espacial
[Mh] Termos MeSH secundário: Acetilcisteína/uso terapêutico
Antagonistas Adrenérgicos beta/uso terapêutico
Medicina Aeroespacial
Antagonistas de Receptores de Angiotensina/uso terapêutico
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico
Anti-Inflamatórios não Esteroides/uso terapêutico
Bloqueadores dos Canais de Cálcio/uso terapêutico
Cloridrato de Fingolimode/uso terapêutico
Depuradores de Radicais Livres/uso terapêutico
Seres Humanos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
Hipoglicemiantes/uso terapêutico
Imunossupressores/uso terapêutico
Metformina/uso terapêutico
Pentoxifilina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Angiotensin Receptor Antagonists); 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Calcium Channel Blockers); 0 (Free Radical Scavengers); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Hypoglycemic Agents); 0 (Immunosuppressive Agents); 0 (Radiation-Protective Agents); 9100L32L2N (Metformin); G926EC510T (Fingolimod Hydrochloride); SD6QCT3TSU (Pentoxifylline); WYQ7N0BPYC (Acetylcysteine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM; S
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE
[do] DOI:10.3357/AMHP.4735.2017


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[PMID]:28583366
[Au] Autor:Wang Y; Dong L; Li J; Luo M; Shang B
[Ad] Endereço:Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, China.
[Ti] Título:Pentoxifylline induces apoptosis of HepG2 cells by reducing reactive oxygen species production and activating the MAPK signaling.
[So] Source:Life Sci;183:60-68, 2017 Aug 15.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Pentoxifylline (PTX) is a methylxanthine derivative and has potent anti-tumor activity. This study aimed at investigating the anti-HCC effects of PTX and associated molecular mechanisms. MAIN METHODS: The effects of varying doses of PTX on viability, cell cycle and apoptosis of HepG2 cells were determined by MTT and flow cytometry, respectively. The effects of PTX on the production of reactive oxygen species (ROS), expression of pro- and anti-apoptotic regulators and activation of the MAPK signaling in HepG2 cells were analyzed by flow cytometry and Western blot assays. The effects of PTX on the growth of implanted HepG2 cells and their apoptosis in mice were examined. KEY FINDINGS: Our results indicated that PTX inhibited proliferation of HepG2 cells and induced HepG2 cell cycle arrest at G0/G1 phase and apoptosis in a dose- and time-dependent manner. Treatment with PTX reduced levels of ROS and Bcl-X expression, but increased caspase 3 and caspase 9 expression and JNK and ERK1/2 phosphorylation in HepG2 cells. Pre-treatment with n-acetyl-l-cysteine (NAC), a ROS scavenger, enhanced PTX-mediated cell cycle arrest, apoptosis and the JNK and ERK MAPK activation, while pre-treatment with SP600125 or PD98509 attenuated PTX-mediated effects in HepG2 cells. Treatment with PTX inhibited the growth of implanted HCC and promoted HCC apoptosis in mice. SIGNIFICANCE: Our data demonstrate that PTX inhibits proliferation of HepG2 cells and induces HepG2 cell apoptosis by attenuating ROS production and enhancing the MAPK activation in HepG2 cells.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Carcinoma Hepatocelular/tratamento farmacológico
Neoplasias Hepáticas/tratamento farmacológico
Pentoxifilina/farmacologia
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/administração & dosagem
Apoptose/efeitos dos fármacos
Western Blotting
Carcinoma Hepatocelular/patologia
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Citometria de Fluxo
Células Hep G2
Seres Humanos
Neoplasias Hepáticas/patologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Pentoxifilina/administração & dosagem
Fatores de Tempo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Reactive Oxygen Species); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170607
[St] Status:MEDLINE


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[PMID]:28529150
[Au] Autor:Yalcin-Ulker GM; Cumbul A; Duygu-Capar G; Uslu Ü; Sencift K
[Ad] Endereço:Assistant Professor, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Okan University, Istanbul, Turkey. Electronic address: gmerveyalcin@gmail.com.
[Ti] Título:Preventive Effect of Phosphodiesterase Inhibitor Pentoxifylline Against Medication-Related Osteonecrosis of the Jaw: An Animal Study.
[So] Source:J Oral Maxillofac Surg;75(11):2354-2368, 2017 Nov.
[Is] ISSN:1531-5053
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The aim of this experimental study was to investigate the prophylactic effect of pentoxifylline (PTX) on medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: Female Sprague-Dawley rats (n = 33) received zoledronic acid (ZA) for 8 weeks to create an osteonecrosis model. The left mandibular second molars were extracted and the recovery period lasted 8 weeks before sacrifice. PTX was intraperitoneally administered to prevent MRONJ. The specimens were histopathologically and histomorphometrically evaluated. RESULTS: Histomorphometrically, between the control and ZA groups, there was no statistically significant difference in total bone volume (P = .999), but there was a statistically significant difference in bone ratio in the extraction sockets (P < .001). A comparison of the bone ratio of the ZA group with the ZA/PTX group (PTX administered after extraction) showed no statistically significant difference (P = .69), but there was a statistically significant difference with the ZA/PTX/PTX group (PTX administered before and after extraction; P = .008). Histopathologically, between the control and ZA groups, there were statistically significant differences for inflammation (P = .013), vascularization (P = .022), hemorrhage (P = .025), and regeneration (P = .008). Between the ZA and ZA/PTX groups, there were no statistically significant differences for inflammation (P = .536), vascularization (P = .642), hemorrhage (P = .765), and regeneration (P = .127). Between the ZA and ZA/PTX/PTX groups, there were statistically significant differences for inflammation (P = .017), vascularization (P = .04), hemorrhage (P = .044), and regeneration (P = .04). CONCLUSION: In this experimental model of MRONJ, it might be concluded that although PTX, given after tooth extraction, improves new bone formation that positively affects bone healing, it is not prophylactic. However, PTX given before tooth extraction is prophylactic. Therefore, PTX might affect healing in a positive way by optimizing the inflammatory response.
[Mh] Termos MeSH primário: Doenças Maxilomandibulares/induzido quimicamente
Doenças Maxilomandibulares/prevenção & controle
Osteonecrose/induzido quimicamente
Osteonecrose/prevenção & controle
Pentoxifilina/uso terapêutico
Inibidores de Fosfodiesterase/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Feminino
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phosphodiesterase Inhibitors); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:AIM; D; IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE



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